In the development of insulin formulations suitable for treatment of diabetes mellitus, it became desirable to alter the characteristics of insulin to prolong its blood-sugar-lowering effect. It was discovered that this could be achieved by conversion of the insulin to a complex which was only partly soluble at the pH of body fluids but which, over an extended period of time, would dissociate with release of insulin. The result is much less rapid insulin absorption.
When insulin is mixed with a properly buffered solution containing protamine, a protamine-insulin precipitate results which has poor solubility and therefore is only slowly absorbed from body tissue. As a result of this finding, several protamine-containing commercial proinsulins are available, including protamine zinc insulin (PZI) and NPH insulin. Either of these insulins, upon subcutaneous injection makes available a depot of supply from which insulin is slowly made available and paid out into the body fluids.
Due to the large quantities of protamine-containing insulin formulations that are produced for use by diabetics, it is natural that certain amounts are returned for any of several reasons, including, for example, outdating, lack of refrigeration, and miscellaneous cosmetic defects. It is highly desirable to have a facile and efficient method available for recovering high purity insulin from formulations containing the protamine-insulin complex. Such insulin then could be re-processed and formulated for distribution to diabetics.
An examination of the literature indicates that, although it contains in abundance papers directed to the extraction and purification of insulin from pancreas glands, it fails to address methods for recovering insulin from protamine-insulin complexes. It is to such a method that this invention is directed.